1. Field of the Invention
The present invention relates to biocarriers and method of using the biocarriers.
2. Description of the Prior Art
To minimize drug degradation and loss, to prevent harmful side-effects and to increase drug bioavailability and the fraction of the drug accumulated in required zone, various drug delivery and drug targeting systems are currently developed or under development. Among drug carriers one can name soluble polymers, microparticles made of insoluble or biodegradable natural and synthetic polymers, microcapsules, cells, cell ghosts, lipoproteins, liposomes, and micelles. Those carriers can be made slowly degradable, stimuli-reactive (for example, pH- or temperature-sensitive), and even targeted (for example, by conjugating them with specific antibodies against certain characteristic components of the area of interest).
Micelles as drug carriers are able to provide a set of unbeatable advantages—they can solubilize poorly soluble drugs and thus increase their bioavailability, they can stay in the mammalian blood (e.g. human blood) long enough providing gradual accumulation in the required area, their size permits them to accumulate in body regions with leaky vasculature, they can be targeted by attachment of a specific ligand to the outer surface, and they can be prepared in large quantities easily and reproducibly. Being in a micellar form, the drug is well protected from possible inactivation under the effect of biological surroundings, it does not provoke undesirable side effects, and its bioavailability is usually increased.
The micelle is structured in such a way that the outer surface of the micelle exposed into the aqueous surrounding consists of components that are hardly reactive towards blood or tissue components. This structural peculiarity allows micelles to stay in the blood (tissues) rather long without being recognized by certain proteins and/or phagocytic cells. This longevity is an extremely important feature of micelles as drug carriers.
In another aspect, gene therapy employs a viral or non-viral vector to carry the therapeutic DNA into the target cells. Viral systems present high delivery and expression efficiencies as they are natural highly evolved DNA carriers. However, safety issues, little DNA carrying capacity, and production problems of the viral vectors have limited their clinical use. Non-viral vectors present advantages including: non-pathogenic, non-immunogenic, larger DNA carrying capacity, and less expensive and easier to produce. However, their transfection and expression efficiencies are relatively low compared to viral systems.
Among the non-viral vectors, the oppositely charged polycation and DNA interact to form a nanometric size polyplex to encapsulate the DNA and protect it before into the cell. The properties of polyplexes are easier to be controlled than other non-viral vectors; however, many polyplexes, such us PEI-PLL, poly(diallyl-dimethyl-ammonium chloride) (DADMAC), diethylaminoethyl-dextran (DEAE-dextran), and poly(vinyl pyridinium bromide)(PVPBr), have been found to be toxic. Moreover, it is found that many polyplexes in contact with red blood cells will highly damage to plasma membranes.
Accordingly, it would be advantageous to develop new biocarriers with high and controllable blood compatibility for medical applications, such as to be employed to construct low cytotoxicity non-viral carriers for efficiently delivering vector DNA to target cells.